Receptor-Mediated Changes in Hepatocyte Phosphoinositide Metabolism
Hepatocytes respond to a variety of extracellular stimuli which evoke intracellular metabolic changes. Among these, glucagon, isoproterenol, and other β-adrenergic receptor agonists act via elevation of cAMP levels, which leads to activation of glycogen phosphorylase and a resultant onset of glycogenolysis. However, another group of stimuli, which includes α1 adrenergic agonists, vasopressin, and angiotensin II, each acting at a distinct cell surface receptor, enhances glycogen phosphorylase activity in rat hepatocytes. The mechanism is cAMP independent and involves a rapid rise in free cytosolic Ca2+ [6,10,31]. The mechanism of Ca2+ mobilization is unsettled, but cumulative evidence suggests that the ion is released from at least one and possible several intracellular sites. An increase in cytosolic Ca2+ may also constitute a step in the initiation of other cellular events such as inactivation of glycogen synthetase and stimulation of potassium fluxes across the plasma membrane . The release of Ca2+ into the cytosol appears to be followed by extensive net uptake of the ion from the external medium, perhaps to replenish depleted intracellular stores.
KeywordsPhosphatidic Acid Glycogen Phosphorylase Inositol Phospholipid Inositol Polyphosphates Phosphoinositide Metabolism
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